The broad, long term objective of the proposed grant is to develop an integrated multimodal intravascular imaging system that combines intravascular optical coherence tomography (OCT), ultrasound (US), and phase-resolved acoustic radiation force optical coherence elastography (ARF-OCE). The multimodal intravascular imaging system is unique in that it combines the advantages of the high spatial resolution of OCT, the broad imaging depth of US, and the biomechanical contrast of ARF-OCE. Visualizing plaques to help understand the progression of disease and to aid in diagnosis and treatment is highly desirable. Both in vitro and in vivo studies have shown that fatty tissue has a higher strain than fibrous plaques and that vulnerable plaques are in high strain areas surrounded by low strain areas. More recent studies have pointed to the vulnerability and the risk of rupturing of plaques being related to the stress on the fibrous cap, the cap thickness, arterial remodeling, and the composition of the plaques. Therefore, it is important to measure the biomechanical properties of the artery tissue to monitor the atherosclerosis to reduce the rupture proneness of an artery and to correlate with clinical symptoms and inflammation markers. The combined multimodal vascular imaging system will permit cross-sectional visualization of vasculature with high spatial resolution, broad imaging depth, and high biomechanical sensitivity, which is not possible by any of these technologies alone. The integrated OCT/US/ARF-OCE will provide the physician with a powerful tool for imaging, diagnosing, and managing vulnerable plaques. Furthermore, this multi-modal imaging strategy in a single system permits the use of a single disposable guide wire and catheter, thereby reducing costs to hospitals and patients, and improving prognosis by early detection. The specific aims are: (1) Design and develop an integrated intravascular OCT/US/ARF-OCE imaging probe, (2) Design and develop an integrated intravascular OCT/US/ARF-OCE system, (3) Develop algorithms for image reconstruction and biomechanical property determination, (4) Image cardiovascular plaques in rabbits and porcine animal models using an integrated OCT/US/ARF-OCE system, and (5) Demonstrate clinical applications of the integrated multimodal imaging system in pilot in vivo human subject studies. The proposed research is expected to have significant impact in the earlier detection, prevention, and treatment of cardiovascular diseases. PHS 398